Enhanced dissolution and bioavailability of revaprazan using self-nanoemulsifying drug delivery system. (21st April 2022)

• Record Type: Journal Article
• Authors: Goo, Yoon Tae; Sa, Cheol-Ki; Kim, Min Song; Sin, Gi Hyeong; Kim, Chang Hyun; Kim, Hyeon Kyun; Kang, Myung Joo; Lee, Sangkil; Choi, Young Wook
• Is Part Of: Pharmaceutical development and technology. Volume 27:Number 4(2022)
• Page Start: 414
• Page End: 424
• Publication Date: 2022-04-21
• Subjects: Self-nanoemulsifying drug delivery system -- revaprazan -- oral bioavailability -- lymphatic transport -- cycloheximide; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.1080/10837450.2022.2070644
• Languages: English
• ISSNs: 1083-7450

Abstract

Abstract: A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the dissolution and oral bioavailability (BA) of revaprazan (RVP). Various SNEDDSs containing 200 mg of RVP were formulated using Capmul MCM, Tween 80, and Brij L4, and they were characterized according to their size, polydispersity index, and dissolution behavior. Dissolution rates of all SNEDDS formulations significantly ( p < 0.05) improved with the formation of nanoemulsion with monodispersity. Formulation D resulted in RVP dissolution exceeding 70% at 2 h. Compared to raw RVP, SNEDDS exhibited a 4.8- to 7.4-fold improved effective permeability coefficient (Peff ) throughout the intestine in the in situ single pass intestinal permeability study and a 5.1-fold increased oral BA in the in vivo oral absorption assessment in rats. To evaluate the degree of lymphatic uptake, cycloheximide (CYC), a chylomicron flowing blocker, was pretreated prior to the experiment. This pretreatment barely affected the absorption of raw RVP; however, it greatly influenced the absorption of SNEDDS, resulting in an approximately 40% reduction in both the Peff value and oral BA representing lymphatic transport. Thus, we suggest that the SNEDDS formulation is a good candidate for improving oral absorption of RVP through enhanced lymphatic uptake. Graphical Abstract: UF0001